Novel PET Systems and Image Reconstruction with Actively Controlled Geometry

Positron Emission Tomography (PET) provides in vivo measurement of imaging ligands that are labeled with positron emitting radionuclide. Since its invention, most PET scanners have been designed to have a group of gamma ray detectors arranged in a ring geometry, accommodating the whole patient body. Virtual Pinhole PET incorporates higher resolution detectors being placed close to the Region-of-Interest (ROI) within the imaging Field-of-View (FOV) of the whole-body scanner, providing better image resolution and contrast recover. To further adapt this technology to a wider range of diseases, we proposed a second generation of virtual pinhole PET using actively controlled high resolution detectors integrated on a robotic arm. When the whole system is integrated to a commercial PET scanner, we achieved positioning repeatability within 0.5 mm. Monte Carlo simulation shows that by focusing the high-resolution detectors to a specific organ of interest, we can achieve better resolution, sensitivity and contrast recovery. In another direction, we proposed a portable, versatile and low cost PET imaging system for Point-of-Care (POC) applications. It consists of one or more movable detectors in coincidence with a detector array behind a patient. The movable detectors make it possible for the operator to control the scanning trajectory freely to achieve optimal coverage and sensitivity for patient specific imaging tasks. Since this system does not require a conventional full ring geometry, it can be built portable and low cost for bed-side or intraoperative use. We developed a proof-of-principle prototype that consists of a compact high resolution silicon photomultiplier detector mounted on a hand-held probe and a half ring of conventional detectors. The probe is attached to a MicroScribe device, which tracks the location and orientation of the probe as it moves. We also performed Monte Carlo simulations for two POC PET geometries with Time-of-Flight (TOF) capability. To support the development of such PET systems with unconventional geometries, a fully 3D image reconstruction framework has been developed for PET systems with arbitrary geometry. For POC PET and the second generation robotic Virtual Pinhole PET, new challenges emerge and our targeted applications require more efficiently image reconstruction that provides imaging results in near real time. Inspired by the previous work, we developed a list mode GPU-based image reconstruction framework with the capability to model dynamically changing geometry. Ordered-Subset MAP-EM algorithm is implemented on multi-GPU platform to achieve fast reconstruction in the order of seconds per iteration, under practical data rate. We tested this using both experimental and simulation data, for whole body PET scanner and unconventional PET scanners. Future application of adaptive imaging requires near real time performance for large statistics, which requires additional acceleration of this framework

Accurate,robust and harmonized implementation of morpho-functional imaging in treatment planning for personalized radiotherapy

In this work we present a methodology able to use harmonized PET/CT imaging in dose painting by number (DPBN) approach by means of a robust and accurate treatment planning system. Image processing and treatment planning were performed by using a Matlab-based platform, called CARMEN, in which a full Monte Carlo simulation is included. Linear programming formulation was developed for a voxel-by-voxel robust optimization and a specific direct aperture optimization was designed for an efficient adaptive radiotherapy implementation. DPBN approach with our methodology was tested to reduce the uncertainties associated with both, the absolute value and the relative value of the information in the functional image. For the same H&N case, a single robust treatment was planned for dose prescription maps corresponding to standardized uptake value distributions from two different image reconstruction protocols: One to fulfill EARL accreditation for harmonization of [18F]FDG PET/CT image, and the other one to use the highest available spatial resolution. Also, a robust treatment was planned to fulfill dose prescription maps corresponding to both approaches, the dose painting by contour based on volumes and our voxel-by-voxel DPBN. Adaptive planning was also carried out to check the suitability of our proposal. Different plans showed robustness to cover a range of scenarios for implementation of harmonizing strategies by using the highest available resolution. Also, robustness associated to discretization level of dose prescription according to the use of contours or numbers was achieved. All plans showed excellent quality index histogram and quality factors below 2%. Efficient solution for adaptive radiotherapy based directly on changes in functional image was obtained. We proved that by using voxel-by-voxel DPBN approach it is possible to overcome typical drawbacks linked to PET/CT images, providing to the clinical specialist confidence enough for routinely implementation of functional imaging for personalized radiotherapy.Junta de Andalucía (FISEVI, reference project CTS 2482)European Regional Development Fund (FEDER

Role of noninvasive molecular imaging in determining response

The intersection of immunotherapy and radiation oncology is a rapidly evolving area of preclinical and clinical investigation. The strategy of combining radiation and immunotherapy to enhance local and systemic antitumor immune responses is intriguing yet largely unproven in the clinical setting because the mechanisms of synergy and the determinants of therapeutic response remain undefined. In recent years, several noninvasive molecular imaging approaches have emerged as a platform to interrogate the tumor immune microenvironment. These tools have the potential to serve as robust biomarkers for cancer immunotherapy and may hold several advantages over conventional anatomic imaging modalities and contemporary invasive tissue acquisition techniques. Given the key and expanding role of precision imaging in radiation oncology for patient selection, target delineation, image guided treatment delivery, and response assessment, noninvasive molecular-specific imaging may be uniquely suited to evaluate radiation/immunotherapy combinations. Herein, we describe several experimental imaging-based strategies that are currently being explored to characterize in vivo immune responses, and we review a growing body of preclinical data and nascent clinical experience with immuno-positron emission tomography molecular imaging as a putative biomarker for cancer immunotherapy. Finally, we discuss practical considerations for clinical translation to implement noninvasive molecular imaging of immune checkpoint molecules, immune cells, or associated elements of the antitumor immune response with a specific emphasis on its potential application at the interface of radiation oncology and immuno-oncology

Early Diagnosis of Alzheimer's Disease by NIRF Spectroscopy\ud and Nuclear Medicine\ud

Novel approaches to Early Diagnosis of Alzheimer's Disease by NIRF Spectroscopy and Nuclear Medicine are presented and related cognitive, as well as molecular and cellular, models are critically evaluated.\u